Our studies based on Thymoglobulin, cyclosporine, azathioprine and prednisone resulted in a 1-year rejection rate of 4% and 3-year graft survival of 95%. Use of tacrolimus, compared to cyclosporine, has been associated with lower rejection rates and better graft survival. The incidence of polyoma virus infection may increase with tacrolimus. Polyoma virus has a 60-80% seroprevalence in the general population and reactivation after transplant is common. It is an important cause of graft dysfunction with graft loss in 50% of cases. The incidence, natural history, the role of tacrolimus or cyclosporine on the incidence of reactivation; the relationship of viruruia, viremia, invasive disease and renal dysfunction; and whether other viruses are co-factors for polyoma infection are unknown. Thus, this study has 3 Specific Aims. Aim 1: To determine the incidence, natural history and associated factors of polyoma infection from the time of transplant and over 1-year in a large cohort (n=250) of new renal transplant recipients monitored with PCR of urine, plasma, and whole blood weekly for 16 weeks and at months 4, 5, 6, 9 and 12, in patients treated with tacrolimus or cyclosporine. Aim 2: To determine the relationship among tissue, blood and urine polyoma-PCR and renal allograft pathology, by analyzing conventional histopathology, immunohistochemistry, in situ hybridization, and tissue, blood and urine-PCR for polyoma in renal transplant recipients with graft dysfunction. Aim 3: To determine whether active polyoma virus infection is a co-factor in the 10-20% of patients who develop active CMV, HHV-6, or HHV-7 after discontinuation of oral ganciclovir prophylaxis compared to the 80-90% of patients at risk who do not develop CMV disease.The candidate is a patient-oriented researcher and an Established Investigator for the American Heart Association and a Young Investigator for the American Society of Transplantation. He has or currently mentored 13 patient-oriented researchers. This award and project will allow him to improve his own patient-oriented research and mentoring capabilities. It will allow him to increase the number and more formally mentor the patient-oriented training of fellows and junior faculty.